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Squidward is happy on this day because it is Sunday! So on Sunday in Bikini Bottom, Squidward walks out of his home and slips on Gary's slime-trail. He gets mad and builds a fence of cheap splintery wood to protect him, and Gary the Snail bites him. Soon after that Patrick enters SpongeBob's House and tells SpongeBob about Mad Snail Disease. SpongeBob becomes a bit worried because Gary was acting strange. Later, Squidward asks SpongeBob if Gary has had all of his shots. SpongeBob says that he has forgotten to give him his "mad snail disease" shot, a disease Patrick had mentioned to SpongeBob beforehand. Just then, Gary runs off and starts to bite everybody in sight. Patrick tells SpongeBob and Squidward about the symptoms of the disease, one of which at the end is turning into a zombie. Bikini Bottom gets burned and wrecked as everybody scrambles to evacuate the city this becomes a huge issue in the whole town. Soon, almost everybody gets bitten and believes they have turned into zombies. Those who have not fled are trapped in the Krusty Krab. SpongeBob tries to get in, but they believe he is a zombie. He slips through the doors. The citizens believe that Patrick and SpongeBob are zombies. Then people are accusing of people to be zombies...

Just then Gary comes in, much to the frightening of the civilians. Gary bites SpongeBob. A Bikini Bottom doctor, Dr. Gill Gilliam, comes inside and says that the disease is just an urban legend and Gary was just suffering from a tree-sized splinter in his foot from Squidward's large wooden fence. The episode ends with Gary biting Mr. Krabs although this was unknown why....

The plot of this episode appears to be a parody of classic zombie movies such as 28 Days Later, Night of the Living Dead, Dawn of the Dead, Zombieland and the Left 4 dead video game series.

Around the end, most of the Bikini Bottomites who were not "infected" by Mad Snail Disease fled and locked themselves in the Krusty Krab. This is what happened in Dawn of the Dead.

This episode is similar to the viral outbreak in the Resident Evil series, when Raccoon City is infected with a virus and all of the citizens became zombies. Also, when SpongeBob is first attacked by the zombies, some of the zombies are dressed in police uniform, which is similar to the zombies in Resident Evil 2.

Mad Snail Disease is a parody of Mad Cow Disease, or BSE, which is a fatal brain disease seen in cattle. The symptoms for snails are similar to rabies.

Patrick says to Squidward that he has severely untrimmed toenails but Squidward does not have human-like feet, he has tentacles. This can also be seen in the episode Giant Squidward.

This is the second time Mr.Krabs' butt is bitten. The first was Clams.

The episode's title is a parody of the phrase Once Bitten, Twice Shy.

Dr. Gill Gilliam's name seems to be taken from the name of Squidward's rival, Squilliam Fancyson. Squilliam and Gilliam both rhyme with William.

In this episode, Dr. Gill Gilliam is shown with orange skin. In other episodes, he is purple.

Sandy is absent from this episode.

Gary and Squidward get along in most episodes after this.

There is a fish that is wearing scuba gear, but in later scenes he is missing.

Medley and his wife are seen in a traffic jam to get out of the city.

Somehow, Bikini Bottom lights on fire whenever there is a riot either due to the fish starting one or something they are scared of starting one. For example, in Wormy they were scared of Wormy so the city got caught on fire.